The objective of this project is to investigate the role of the podocyte as a structural element within the glomerulus. This function may be undermined in pathologic states associated with glomerular hypertension, resulting in podocyte injury and glomerulosclerosis. Thus, defining the role of the podocyte in maintaining glomerular structure in the face of mechanically unfavorable environments will help identify new approaches to delay kidney disease progression to end stage renal failure. The first phase of this project will characterize the potential of the podocyte to maintain a basal level of intracellular tension between attachment sites at the cellular processes, using cultured human podocytes grown on a well-characterized force measurement substrate. The next phase will investigate how the force-generating properties of podocytes change when the function of certain cytoskeletal elements, particularly myosin contractile proteins, is interfered with. Candidate myosins will be identified using publicly available serial analysis of gene expression (SAGE) data, and the effect of pharmacologic agents and mRNA interference upon the presence and mechanical function of these myosins will be assessed.